PROJECT SUMMARY Invasive cervical cancer (ICC) is the leading cause of cancer-related deaths among women in sub-Saharan Africa. The burden of ICC can be reduced with the early detection of pre-cancerous lesions through screening. Previous studies have shown regular pap and/or human papillomavirus (HPV)?based screening decreases ICC incidence and mortality by at least 80%. However, challenges remain in screening coverage in resource- limited settings. In Kenya, screening coverage is estimated at only 3.2% among women aged 18-69 years. One reason for low screening coverage in resource-limited areas is the need for health facility-level pelvic examination to collect cervico-vaginal specimens. Unfortunately, healthcare infrastructure in many resource- limited settings is characterized by poorly equipped health facilities and a shortage of skilled health providers. A novel approach to address this gap in healthcare services in low-resource settings is to use home self- collection devices for high-risk (hr) HPV testing. Previous studies have established the equivalency between self- and physician-collected samples for hr-HPV testing based on similar sensitivities for the detection of hr- HPV DNA and high-grade cervical intraepithelial neoplasia stage 2 or above (CIN2+). However, little attention has been given to the assessment of different self-sampling devices for the detection of hr-HPV mRNA. The evaluation of hr-HPV mRNA in cervical cancer self-screening is crucial as E6 and E7 mRNA have been identified as prognostic biomarkers that can most accurately predict progression to ICC. This research-training plan will provide the fellowship applicant an opportunity to further develop the theoretical, analytical and research experience needed to assess validity and cost-effectiveness of novel cancer screening devices in a limited resource setting, which will be examined as part of the dissertation research. This dissertation research will address the following specific aims: Aim 1. Compare the prevalence of abnormal results by different cervical cancer screening tests: i. self-collected dry HPV mRNA ?dry self?, ii. self-collected wet HPV mRNA ?wet self,? iii. physician-collected HPV mRNA, iv. visual inspection with acetic acid (VIA) and v. conventional cytology; Aim 2: Determine the clinical validity of hr-HPV mRNA detection assays from self-collected (?wet self? and dry self?) vaginal specimens, compared to hr-HPV mRNA detection from physician-collected cervical specimens; VIA; and conventional cytology for CIN2+ detection as the clinical endpoint; and Aim 3: Evaluate and compare the cost-effectiveness of a lifetime screen using i. ?wet self?, ii. ?dry self?, iii. physician HPV- detection methods, iv. VIA, and v. conventional cytology for the detection of CIN2+. Through these aims and activities outlined in the research training plan, the applicant will obtain training in epidemiology and health services research to further understand the implementation of research to improve cancer control in under- resource settings. With the successful completion of the above aims, the applicant intends to identify ?dry self? test as a clinically valid and cost-effective method for cervical cancer self-screening.